THE BIOLOGY OF STEM CELLS

Melissa Henriksen, PhD

Clare Boothe Luce Assistant Professor

Biological Sciences

The Biology of All Cells

DNA mRNA Proteintranscription translation

5’cap

3’polyA tail

Gene Expression

DNA mRNA Proteintranscription translation

Different Cell Types

Same DNA Different Gene Expression

pancreatic bone neurons ES

The Biology of Stem Cells

• Embryonic Stem Cells• The Concept of Potency• Adult Stem Cells• Advances in Stem Cell Science

Human Embryogenesis

Embryonic Stem Cells & IVF

Stem Cell Research

Commitment in Embryogenesis

• Cell Commitment• Cells make “Decisions”• “Decisions” determine

cell’s fate• Thought to be irreversible

The Blastocyst

Culturing Embryonic Stem Cells

What is a Stem Cell?

Two identical daughters Self-renewal Differentiate

Somatic Cell Stem Cell

PotencyThe range of commitment options available to a cell

• Totipotent

• Pluripotent

• Multipotent

• Oligopotent

• Unipotent

Potency

Potency

Pluripotent Multipotent

Adult Stem Cell Differentiation

Adult Stem Cell Plasticity

Amniotic Fluid-derived Stem Cells

PotencyThe range of commitment options available to a cell

• Totipotent

• Pluripotent

• Multipotent

• Oligopotent

• Unipotent

Potency

Embryonic

Adult

Amniotic

Somatic Cell Nuclear Transfer

DOLLY

1997

“Decisions”not irreversible

SCNT & Animals

SCNT & Humans

SCNT & Humans

?

SCNT & Cancer Cells

start with cancer cell

Breast cancerLeukemia

LymphomaMelanoma

Pluripotent Stem Cells

MelanomaTetraploid Complementation

E9.5

Advances in Stem Cell Science

• Avoid ethical issues• Egg donation• Matched stem cells• Develop cell-based

disease models• Understand the

science

• Parthenogenesis • 8-cell Blastomere • Altered Nuclear

Transfer• Molecular

Reprogramming

Parthenogenesis

• Asexual Reproduction• Normal in Reptiles; Not seen

in Mammals• Trick human eggs to

undergo in the lab• Immunologically matched to

egg donor• “Universal Donor?”• Not Viable• No “Potential Human Being”

8-cell Blastomere

• PGD - Preimplantation Genetic Diagnosis

• 1 of 8 cells removed• ACT cultured embryonic

stem cell line from one cell

Altered Nuclear Transfer

• Idea suggested by President’s Council on Bioethics

• Apply a genetic trick in the somatic cell nucleus

• Blastocyst generated is not viable• No “Potential Human Being” • Proof-of-Principle demonstrated in mice by

scientists at MIT’s Whitehead Institute

Molecular Reprogramming

Potency

Goal: Manipulate a somatic cell’s potency

• Totipotent

• Pluripotent

• Multipotent

• Oligopotent

• Unipotent

somatic cell

Molecular Reprogramming

• Cell Fusion

• Cell Extract

• Cell Explantation

• Add Four Factors

pluripotent

pluripotent

+ 4 Factors

pluripotent

x pluripotent

Bibliography

• AFS• SCNT

– Cancer cells

• ANT• Blastomere• Parthenogenesis• Molecular Reprogramming

– Cell Fusion– Cell Extract– Cell Explantation– Defined Factors